Prior art methods for labeling antibodies with technetium-99m used stannous chloride as a reducing agent to generate sulfhydral groups on antibodies. At the same time the antibodies were contacted with technetium and a chelator, typically DTPA, to achieve binding of the technetium to the antibodies, while scavenging unbound technetium with the DPTA present in the reaction medium.
Paik et al. reported that carrying out technetium-99m labeling in presence of excess DTPA (MoAb:DTPA=1:10) one could selectively attach technetium-99m to high affinity sites. Stannous chloride was present in 10-fold excess over the protein. Their typical reaction conditions (Paik et al.) are as follows: EQU [MoAb]=10 .mu.m EQU [SnCl.sub.2 ]=100 .mu.m EQU [DTPA]=100 .mu.m
Selective binding to high affinity sites, however, was obtained only under experimental conditions where both DTPA and antibody were competing for the reduced technetium ion. Paik et al. reported that about 10 times molar excess of DTPA was required to avoid technetium-99m binding to low affinity sites. Unfortunately the presence of excess DTPA resulted in reduced specific activity (.sup..about. mCi/mg). Following their procedures with antibody 88BV59, an IgG.sub.3, the yield was only 0.01-0.5 mCi/mg.